Evidence for metabotropic function of epithelial nicotinic cholinergic receptors in rat colon

British Journal of Pharmacology
Lena LottigM Diener

Abstract

ACh exerts its actions via nicotinic (nAChR) and muscarinic receptors. In the peripheral nervous system, ionotropic nAChR mediate responses in excitable cells. However, recent studies demonstrate the expression of nAChR in the colonic epithelium, which are coupled to an induction of Cl- secretion via activation of the Na+ -K+ -pump. In order to find out whether these epithelial nAChR function as ionotropic receptors, intracellular microelectrode and imaging experiments were performed in isolated crypts from rat colon. Apically permeabilized epithelia were used to measure pump current across the basolateral membrane. Imaging experiments with the Na+ -sensitive dye SBFI revealed that nicotine induced a decrease in the cytosolic Na+ concentration concomitant with a fall in the cytosolic Ca2+ concentration in about 50% of the cells. as shown in fura-2 experiments. Nicotine hyperpolarized the membrane by 6.4 ± 2.1 mV. These observations contradict the assumption that epithelial nAChR function as ligand-gated non-selective cation channels. The decrease in the cytosolic Na+ concentration was strongly delayed, when the Na+ -K+ -pump was inhibited by scilliroside. Ussing chamber experiments revealed a strong dependence of the nicotine-i...Continue Reading

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Citations

Sep 23, 2020·British Journal of Pharmacology·Praveen KumarMonika I Hollenhorst
May 8, 2021·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Klaus MichelMichael Schemann
Apr 15, 2021·American Journal of Physiology. Cell Physiology·Andrew J NickersonVazhaikkurichi M Rajendran

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